Kinetics of biliary elimination of pentacaine in rats

Pentacaine, a local anaesthetic of the carbanilate type, administered intravenously as 3H-pentacaine, 2 mg kg-1 to rats, was eliminated in the bile mainly in the form of metabolites (20.5 +/- 1.5 per cent of the dose) and as parent drug (0.1 per cent of the dose) within 3 days. In control rats 32.2 +/- 2.5 and 37.8 +/- 2.5 per cent of 3H-dose, representing pentacaine metabolites, were excreted in the urine and faeces, respectively. In bile-duct-cannulated rats 35.7 +/- 6.8, 11.2 +/- 3.4, and 20.5 +/- 1.5 per cent of 3H-dose were excreted in the urine, faeces, and bile, respectively. The high 3H recovered in faeces in animals with diverted bile flow indicated passage of pentacaine metabolites through the intestinal wall. The excretion of pentacaine and its metabolites in bile was an active process, since the ratio bile/plasma concentration rapidly attained values approaching 10. In rats with ligated ureters the biliary elimination of pentacaine and its metabolites was enhanced, compensating for impaired urinary excretion. This was accompanied by increased plasma and brain levels of 3H compared with untreated controls.